Caradonna L, Amati L, Lella P, Jirillo E, Caccavo D
IRCCS for Gastroenterological Diseases, Castellana Grotte, Bari, Italy.
Am J Gastroenterol. 2000 Jun;95(6):1495-502. doi: 10.1111/j.1572-0241.2000.02085.x.
Alteration of mucosal and systemic immune responses may play an important role in the pathogenesis of inflammatory bowel disease (IBD). The aim of this study was to evaluate natural immune responses (i.e., phagocytosis, killing, and antibacterial activity), serum autoantibodies (antineutrophil cytoplasmic antibodies [ANCA] and anti-lactoferrin [LF] antibodies), and plasma endotoxins in patients affected by ulcerative colitis (UC) and Crohn's disease (CD).
Blood samples were obtained from 71 patients with UC, 32 patients with CD, and 32 control subjects. Disease activity was scored using Truelove's criteria in patients with UC and the Crohn's Disease Activity Index (CDAI) in patients with CD. Candida albicans served as a target for evaluation of phagocytosis and killing exerted by polymorphonuclear cells (PMN) and monocytes (MO), whereas Salmonella typhi was used for assessing lymphocyte-mediated antibacterial activity. ANCA were detected by indirect immunofluorescence, whereas anti-LF antibodies were assayed by means of enzyme-linked immunosorbent assay. Plasma endotoxins were measured by Limulus amoebocyte lysate assay.
Phagocytosis and killing exerted by PMN and MO, as well as lymphocyte-mediated antibacterial activity, were significantly reduced (p < 0.0001) in patients affected by UC and CD in comparison with controls, irrespective of either disease activity or treatment. Plasma endotoxins were detected in 12/71 (17%) patients with UC, and in 10/32 (31%) patients with CD. ANCA were present in 42/71 (59%) patients with UC and in 3/32 (9%) patients with CD, whereas anti-LF antibodies were detected in 31 (44%) UC patients and in six (19%) CD patients. No significant differences in phagocytosis and killing exerted by PMN were found between ANCA-positive and ANCA-negative UC patients.
Our data demonstrate an impairment of natural immunity exerted by peripheral blood phagocytes and lymphocytes in patients with UC and CD. ANCA and anti-LF antibodies were present mainly in UC patients but their presence did not affect PMN-mediated phagocytosis and killing. Finally, plasma endotoxins may contribute to the chronic inflammatory status, likely by inducing release of proinflammatory mediators.
黏膜和全身免疫反应的改变可能在炎症性肠病（IBD）的发病机制中起重要作用。本研究旨在评估溃疡性结肠炎（UC）和克罗恩病（CD）患者的天然免疫反应（即吞噬作用、杀伤作用和抗菌活性）、血清自身抗体（抗中性粒细胞胞浆抗体[ANCA]和抗乳铁蛋白[LF]抗体）以及血浆内毒素。
采集71例UC患者、32例CD患者和32例对照者的血样。使用Truelove标准对UC患者进行疾病活动评分，对CD患者使用克罗恩病活动指数（CDAI）进行评分。白色念珠菌作为评估多形核细胞（PMN）和单核细胞（MO）吞噬和杀伤作用的靶标，而伤寒沙门菌用于评估淋巴细胞介导的抗菌活性。通过间接免疫荧光检测ANCA，通过酶联免疫吸附测定法检测抗LF抗体。采用鲎试剂法测定血浆内毒素。
与对照组相比，UC和CD患者中PMN和MO的吞噬和杀伤作用以及淋巴细胞介导的抗菌活性均显著降低（p<0.0001），与疾病活动度或治疗无关。12/71（17%）例UC患者和10/32（31%）例CD患者检测到血浆内毒素。42/71（59%）例UC患者和3/32（9%）例CD患者存在ANCA，而31（44%）例UC患者和6（19%）例CD患者检测到抗LF抗体。ANCA阳性和ANCA阴性的UC患者在PMN的吞噬和杀伤作用方面未发现显著差异。
我们的数据表明，UC和CD患者外周血吞噬细胞和淋巴细胞的天然免疫功能受损。ANCA和抗LF抗体主要存在于UC患者中，但它们的存在并不影响PMN介导的吞噬和杀伤作用。最后，血浆内毒素可能通过诱导促炎介质的释放导致慢性炎症状态。
